Abstract
Prior research suggests that the neurobiological underpinnings of depression include aberrant brain functional connectivity, neurometabolite levels, and hippocampal volume. Chronic restraint stress (CRS) depression model in rats has been shown to elicit behavioral, gene expression, protein, functional connectivity, and hippocampal volume changes similar to those in human depression. However, no study to date has examined the association between behavioral changes and brain changes within the same animals. This study specifically addressed the correlation between the outcomes of behavioral tests and multiple 9.4 T magnetic resonance imaging (MRI) modalities in the CRS model using data collected longitudinally in the same animals. CRS involved placing young adult male Sprague Dawley rats in individual transparent tubes for 2.5 h daily over 13 d. Elevated plus maze (EPM) and forced swim tests (FSTs) confirmed the presence of anxiety-like and depression-like behaviors, respectively, postrestraint. Resting-state functional MRI (rs-fMRI) data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. Proton magnetic resonance spectroscopy revealed decreased sensorimotor cortical glutamate (Glu), glutamine (Gln), and combined Glu-Gln (Glx) levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume. Importantly, these changes parallel those found in human depression, suggesting that the CRS rodent model has utility for translational studies and novel intervention development for depression.
Footnotes
The authors declare no competing financial interests.
This work was supported by The University of Western Australia. B.J.S. is supported by a Forrest Research Foundation Scholarship, an International Postgraduate Research Scholarship, and a University Postgraduate Award. L.A.H. is supported by the Commonwealth Government’s Australian Government Research Training Program Fees Offset. K.W.F. was an Australian National Imaging Facility Fellow, a facility funded by the University, State and Commonwealth Governments. P.E.C. was supported by the National Institute of Mental Health Grant R01 MH113700. J.R. was supported by a Fellowship from MSWA and the Perron Institute for Neurological and Translational Science.
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